1. Field of the Invention
The invention relates to a new process for the production of di-n-propyl-acetic acid from n-butyric acid.
2. Discussion of the Prior Art
Derivatives of di-n-propyl-acetic acid have gained great importance as psychopharmacologic drugs and antiepileptics. Several syntheses for the preparation of the acid have already been described.
In a known process, the starting material is malonic acid diethyl ester which is reacted initially with sodium methylate and then with allyl chloride to form d-allyl-diethyl malonate. Saponification with sodium hydroxide gives the sodium salt of diallyl malonic acid which is thermally decarboxylated to form diallyl acetic acid and subsequently hydrogenated partially to form di-n-propyl-acetic acid. The process requires the use of expensive starting materials which are difficult to handle technically such as sodium methylate and allyl chloride.
Another mode of operation varies a process for the preparation of di-isopropylacetic acid having been described by Sarel, J. Am. Chem. Soc. 78, 5416-5420 (1956). In this process, cyanoacetic acid ester is alkylated in the presence of sodium isopropylate by means of isopropyl iodide. This results in the formation of diisopropyl-cyanoacetic acid ester which is decarboxylated to form diisopropylacetonitrile. In further steps, the diisopropylacetonitrile is converted into diisopropylacetic acid via diisopropylacetic acid amide. The application of this reaction route to the synthesis of di-n-propylacetic acid results, however, in total yields of only 10 to 40% and, therefore, is commercially unattractive.
East German (DDR) Patent No. 129,776 describes a process for the production of di-n-propylacetic acid which starts from an ester of cyanoacetic acid. Reaction with n-propyl bromide or iodide in the presence of sodium-n-propylate, saponification of the di-n-propyl-cyanoacetic acid ester by means of caustic and acidification result in 2,2-di-n-propylcyanoacetic acid which is decarboxylated to form di-n-propylacetonitrile. The acetonitrile is subsequently converted with aqueous sulfuric acid via the acetamide into di-n-propyl-acetic acid. This process also uses expensive starting materials and requires the use of reaction steps which cannot be carried out continuously. Moreover, since the hydrolysis of acetamide to form the acid is carried out in the presence of sodium nitrite, problems in connection with environmental pollution are encountered.
It is, therefore, an object of this invention to provide a process for the preparation of di-n-propylacetic acid which starts from inexpensive starting materials which are available in commercial amounts at moderate prices, comprises reaction steps which are readily carried out commercially and synthesizes the desired product available in satisfactory yields.
These requirements are surprisingly met by a process for the preparation of di-n-propyl-acetic acid, which comprises the steps of:
A. catalytically reacting n-butyric acid to form heptanone-4 with cleavage of carbon dioxide and water; PA1 B. hydrogenating heptanone-4 in the presence of a catalyst to form heptanol-4; PA1 C. dehydrating heptanol-4 in the presence of an Al.sub.2 O.sub.3 catalyst to form heptene-3; PA1 D. hydroformylating heptene-3 in the presence of a rhodium complex compound as catalyst to form a mixture of 2-propyl pentanal and 2-ethyl hexanal; PA1 E. oxidizing the 2-propyl pentanal/2-ethyl hexanal mixture to form a mixture of di-n-propyl-acetic acid and 2-ethyl hexanoic acid, and PA1 F. separating the mixture of di-n-propyl-acetic acid and 2-ethyl hexanoic acid to recover pure di-n-propyl-acetic acid.
The preparation of ketones from carboxylic acids is a known reaction. In this reaction, 1 molecule of ketone is formed from 2 molecules of an acid with cleavage of carbon dioxide and water. The reaction is usually carried out at temperatures between 300.degree. and 600.degree. C. in the presence of catalysts such as chromium oxide, iron, thorium dioxide and manganese (IV) oxide (see, for example, Methodicum Chemicum, Vol. 5, page 462). The reaction is carried out with a space velocity of 0.25 cu.m/hr.cu.m.
The use of ThO.sub.2 /Al.sub.2 O.sub.3 catalysts has been described specifically for the preparation of heptanone-4 from butyric acid (see, for example, Italian Patent 660 9 10). Since thorium is radioactive, narrow limits are set to the use of catalysts of this kind in industry.
It has been found that the reaction of n-butyric acid to heptanone-4 takes place with particularly good success at 350.degree. to 450.degree. C. in the presence of catalysts which contain lanthanum, e.g., in an amount of 0.2 to 20 weight percent. While values of 70% are generally reported for the selectivity of the ketone formation, it is approximately 100% when using lanthanum catalysts. Thus, n-butyric acid is converted over a catalyst composed of 2% by weight of lanthanum (as La.sub.2 O.sub.3), the balance being Al.sub.2 O.sub.3, into heptanone-4 with a selectivity of &gt;99% at a conversion of about 92%.
In the reaction step which follows, the heptanone-4 is hydrogenated to form the corresponding alcohol, i.e., heptanol-4, whithout previous purification being necessary. The reaction with hydrogen is carried out in the liquid phase in the presence of catalysts at temperatures which are dependent on the kind of the hydrogenation catalyst used. Particularly favorable results are obtained with nickel catalysts which contain 30 to 70% by weight of nickel (based on total catalyst) in addition to a support such as alumina, SiO.sub.2, artificial or natural silicates. Preferred is a catalyst which contains 50 to 60% of nickel in addition to kieselguhr as the support. It requires a reaction temperature of 100.degree. to 200.degree. C. A hydrogen pressure of 80 to 150 bars is suitable. The reaction is performed generally up to 4 hours. With a quantitative conversion of the starting material, heptanol-4 is obtained with a selectivity of 97% and more.
After separation of the hydrogenation catalyst, the alcohol can be subjected to the dehydration reaction directly, i.e., again without previous purification. However, it is desirable in several cases to subject the alcohol previously to a coarse distillation so that it is present in a purity of more than 98%. Dehydration of heptanol-4 to heptanone-3 is carried out in the gaseous phase at temperatures between 200.degree. and 350.degree. C. in the presence of an Al.sub.2 O.sub.3 catalyst in which the alumina is preferably present in the .gamma.-modification. Catalysts which contain about 3% of carbon, e.g., in the form of graphite, and .ltoreq.0.01% of Na.sub.2 O or K.sub.2 O, .ltoreq.0.01% of iron oxide and .ltoreq.0.01% of silica in addition to alumina are used with particular success.
Surprisingly, the dehydration of heptanol takes place in the presence of such catalysts without the formation of isomerization products which are produced to a considerable extent if other catalysts are used. A conversion of more than 95% is achieved at temperatures of 250.degree. to 350.degree. C. and a space velocity of 0.2 to 0.8 cu. m./hr.cu.m. The selectivity for heptene-3 formation is 99%.
The heptene-3 obtained by dehydration of heptanol-4 can be subjected directly to the hydroformylation without previous processing or purification. The reaction is carried out as usual in the presence of carbonyl-forming metals of Group 8 of the Periodic Table. The use of rhodium as catalyst which is contained in the reaction mixture in the form of a rhodium complex which contains phosphine has been found to be particularly advantageous. In practice, heptene, a rhodium salt, e.g., rhodium chloride or rhodium hexanoate, and an aliphatic or aromatic phosphine are charged to a pressure vessel. Examples of suitable phosphines include triphenyl phosphine and especially tributyl phosphine. The molar ratio of rhodium salt to phosphine ranges between 1:50 and 1:150 and the Rh concentration, based on the total reaction mixture, between 10 and 100 ppm. Carbon monoxide and hydrogen are desirably introduced into the reactor in a ratio of 1:1. The reaction takes place at 100.degree. to 180.degree. C. and a pressure of 150 to 300 bars. The carbon monoxide-hydrogen mixture is introduced into the reactor so that the reaction pressure chosen is maintained. The use of rhodium catalysts containing a phosphine as complex ligand has the unexpected result that the olefin is reacted quantitatively to a mixture of 70 to 75% by weight of 2-propyl pentanal and 25 to 30% by weight of 2-ethyl hexanal. By-products by isomerization of the starting olefin are not produced.
The hydroformylation product is processed in known manner by separation of the catalyst and distillation. There results a mixture of about 75% by weight of 2-propyl pentanal and 25% by weight of 2-ethyl hexanal, which contains contaminations only to a minor extent.
This aldehyde mixture is oxidized with oxygen at 20.degree. to 80.degree. C. A molecular oxygen-containing gas is suitable for the oxidation which will be carried out without pressure. Alkali metal salts of higher fatty acids, i.e., monocarboxylic acids having 3 to 12 carbon atoms, e.g., Na-2-ethyl hexanoate, are added as catalyst in an amount of 0.2 to 1.5% by weight, based on the weight of the total reaction mixture. The use of sodium salts as catalysts has the advantage that the reaction proceeds at low temperatures, i.e., in a range of 25.degree. to 35.degree. C., with high selectivity. To obtain pure di-n-propyl acetic acid, separation of the mixture consisting of 2-propyl pentanal and 2-ethyl hexanal by distillation under vacuum has been found to be advantageous. It is desirable to use a column having at least 60 theoretical plates at a reflux ratio of at least 5:1. At pressures of 20 to 50 bars, di-n-propyl acetic acid boils at temperatures between 133.degree. and 154.degree. C.